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1、第四军医大学硕士学位论文TheprotectionofrecombinantproteinTβ4onheartaftermyocardialinfarctionCandidateformaster:WangQiSupervisor:ZhangWeiTutor:LiMengDepartmentofBiopharmaceutics,FourthMilitaryMedicalUniversity,Xi’an710032,ChinaAbstractKeywords:thymosinβ4;concatemer;myocardialinf
2、arctionMyocardialinfarctionisoneofthehighestdeathmorbidityindiseasesofthecardiovascularsystemdiseases.Howtoprotecttheinfarctionareasurroundingischemicmyocardialcells,reducescarformation,improveheartfunctionandpreventheartfailureaftermyocardialinfarctionisanimportant
3、subjectinthestudyofcardiovasculardisease.Tβ4isasmallpeptidecomposedby43aminoacids,whichishighlyconservedinspeciesandwidelydistributedinmostofthecellsexcenttheredbloodcells.Itparticipatesinmanyimportantlifeactivitiesinvolvedinthehumanbodyandcannotonlypromotewoundheal
4、ing,hairgrowth,tissuerepairandangiogenesis,butalsohasanti-inflammatoryeffectandendotoxinshock.Meanwhile,itcanmaintainthedynamicbalanceofcytoskeleton.ThecurrentstudyofTβ4hasenteredthestageofclinicaltrialsforavarietyoftraumaticdiseaseandcardiacprotectionaftermyocardia
5、linfarction.Tβ4usedatthisstagederivesfromchemicalsynthesis.Peptidesynthesisof43amino-5-第四军医大学硕士学位论文acidsislowinefficiency,highinthecost,hasseriousenvironmentalpollution,andhighlyrestrictiveinmassproduction.ThegeneticengineeringproductsofTβ4aredifficulttopurifybecaus
6、eofitssmallermolecules.Intheearlystageofthestudy,weproducedTβ4dimerproteinbyusingengineeringmethod,whichovercomethedefectsofhardnesstoexpressbythechemicalsynthesisofmolecularpeptides.Atthesametime,itsetuptheonestepoftheTβ4dimerproteinpurificationmethod,whichimproved
7、themassproductionprocess.ThepreparationandpurificationmethodsgettwoChineseutilitypatents(ZL200810232709.9;ZL201110376361.2)TheresearchofTβ4dimerproteinpromotingwoundhealingfunctionhaveobtainedmajorfundingofthenationaldrugdiscoveryresearch(2011ZXJ09104-01).Onthebasis
8、oftheabove,thesubjectresearchwillfurtherstudythecardiacprotectioneffectonTβ4dimerproteinaftermyocardialinfarction,anddiscussitsmechanism,s